Over the last two decades, ultrasound (US) has been applied to enhance transdermal drug delivery. This method is called sonophoresis. The physical mechanism of the enhancement is far from being fully understood. It has been shown in our study that 168-kHz continuous US of spatially averaged pressure amplitude of 1.9 x 10(5) Pa induced a new structural state and generated defects (entrapped air pockets) in human stratum corneum specimens. The dimensions of the defects were found to be about 20 microns, large enough to allow the transdermal passage of high-molecular-weight drug molecules that normally elude the unenhanced transdermal drug delivery.